Without limiting the scope of the invention, its background is described in connection with the analysis of nucleic acid, amino acid, small molecular and/or cellular samples, as an example.
Heretofore, in this field, the analysis of biologically relevant samples has been accomplished using techniques that detect the presence of a marker or markers in known and unknown samples. To detect the presence of these markers, techniques such as, e.g., radiolabelling, fluorescence or enzymatic labeling, have been used to detect the presence or absence of binding between a component of the sample and a substrate or matrix on which the appropriate binding group or ligand has been immobilized.
Such systems are described in U.S. Pat. No. 5,817,462, which issued to Garini, et al., and U.S. Pat. No. 5,539,517 issued to Cabib, et al., in which interferometric dispersal and recombination of collimated light is used to detect a light signal. The systems described, however, uses discrete filtering system to detect individual samples. Also, these samples are read with discrete filtering elements that prevent the detection of fluorochromes that have adjacent wavelengths of exitation or transmission.
One such system is described in U.S. Pat. No. 5,744,305, which issued to Fodor, et al., in which a synthetic strategy for creating large scale chemical diversity in an array is described. Solid-phase chemistry, photolabile protecting groups and photolithography are used to obtain a light directed spatially-addressable parallel chemical synthesis. Using binary masking techniques, a reactor system is used that can be used to improve data handling and collection. The system described, however, uses a single light source to detect individual samples. Also, these samples are read only once for full spectral coverage, greatly increasing the throughput time of the system.
Another system and method of detection of samples is described in U.S. Pat. No. 5,424,186 issued to Fodor, et al. A method for synthesizing oligonucleotides on a solid substrate is described. The substrate used in the device described provides for the incorporation of semiconductor structures that are used to detect binding of samples to an array of ligands on the surface of the semiconductor. This "biochip" has been the subject of much attention in the art (See e.g., To Affinity . . . and Beyond, Nature Genetics, Vol. 14, 367-370, 1996). The system, however, is only useful for the detection of the material permanently attached to the surface of the chip. The system also requires an expensive customized reader to provide a limited output.
Yet another system involves the production or arrays on slides by deposition and attachment of DNA or other biological/chemical sample. This array is then interrogated with photolabile unknown samples (DNA, RNA, other biological/chemical) and quantitative detection is done using a fluorescent or chemiluminescent reader. Current readers use filter systems to select the desired light, thus limiting the number and accuracy of the unknown samples being measured.